The influence of immunosuppression on the course and outcome of infection by oncogenic viruses is under study in mice. Two loci, one within the H-2 complex and the other outside this region, were found to influence infection by Type C RNA viruses. Congenic mice could be classified as either susceptible or resistant, according to the H-2 haplotypes. Resistant mice were rendered susceptible to the virus by treatment with either x-radiation or antilymphocyte serum (ALS). Infected, ALS-treated mice had very high titers of virus for months and 75 percent ultimately developed lymphomas. By contrast, resistant mice treated with either virus or ALS alone had low (or undetectable) titers of virus and failed to develop lymphomas. The evidence favors the hypothesis that immunological surveillance of virus-induced neoplasms in a special case of anti-viral immunity.